Generally, stressors induce glucocorticoid release that acts to suppress inflammatory responses, and often leads to immunosuppression. This is not always the case however, as social disruption stress induces glucocorticoid release and elevations in inflammation. Previous work has shown that when social disruption induced glucocorticoid resistance and elevated inflammation in Theiler's virus infection, this was associated with more severe behavioral signs of the disease and reduced viral clearance over time. Glucocorticoids coregulate many cytokines that are implicated by this pattern of results, including the pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha), the interferons (IFN alpha/beta, IFN gamma), and the TH1/Th2 driving cytokines (IL-10, IL-4/IL-12). This proposal will examine the activation of these cytokines during acute Theiler's virus infection and exacerbation due to social disruption. Initial investigation of the necessity and sufficiency of proinflammatory activation will utilize the cytokine with the most pronounced activation change. A battery of behavioral and motor impairment measures due to illness, hierarchy formation as well as molecular, immunological and histological assessments will be used to examine these issues. [unreadable] [unreadable]